ArticleNature communications2022
Reversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 52 citations in OpenAlex.
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- Deficiencies in the Fanconi anemia or homologous recombination pathway enhance the antitumor effects of the hypoxia-activated prodrug CP-506.Molecular therapy. Oncology · 2026Article
- A Clinically Translatable Multimodal Deep Learning Model for HRD Detection from Histopathology Images.Diagnostics (Basel, Switzerland) · 2026Article
- Article
- Emergence of BRCA Reversion Mutations in Prostate Cancer Prior to PARP Inhibitor Exposure: Clinical and Therapeutic Implications.Cancer medicine · 2026Article
- HSP90 buffers deleterious genetic variations in BRCA1.Molecular cell · 2025Article
- Enabling whole genome sequencing analysis from FFPE specimens in clinical oncology.Nature communications · 2025Article
- DNA Methylation in Ovarian and Endometrial Cancers: Predictive and Mechanistic Roles in PARP Inhibitor and ICI Response.Cancer science · 2025Review
- Integrated single-cell whole genome sequencing and spatial transcriptomics reveal latent intra-tumoral heterogeneity in ovarian cancer.bioRxiv : the preprint server for biology · 2025Article
- Routine Tumor Testing for Homologous Recombination Deficiency in Patients With High Grade Epithelial Ovarian Cancer at a Statewide Gynecological Cancer Service in Western Australia: An Observational Study.Cancer reports (Hoboken, N.J.) · 2025Observational
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- Causative Genes of Homologous Recombination Deficiency (HRD)-Related Breast Cancer and Specific Strategies at Present.Current oncology (Toronto, Ont.) · 2025Review
- Challenging the extended phenotype: HRD-negative salivary gland carcinoma in aFrontiers in oncology · 2025Article
- Microhomology-Mediated End-Joining Chronicles: Tracing the Evolutionary Footprints of Genome Protection.Annual review of cell and developmental biology · 2024Review
- Basket Trials: Past, Present, and Future.Annual review of cancer biology · 2024Article
- Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer.Molecular cytogenetics · 2024Article
- BRCA1/2 reversion mutations in a pan-cancer cohort.Cancer science · 2024Article
- Telomere-related DNA damage response pathways in cancer therapy: prospective targets.Frontiers in pharmacology · 2024Review
- The Clinical Implications of Reversions in Patients with Advanced Pancreatic Cancer and Pathogenic Variants in BRCA1, BRCA2, or PALB2 after Progression on Rucaparib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- MRE11:p.K464R mutation mediates olaparib resistance by enhancing DNA damage repair in HGSOC.Cell & bioscience · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
The association between loss of BRCA1/2 and a homologous recombination deficiency phenotype is lineage dependent. In BRCA-associated cancers such as breast, ovarian, pancreas and prostate, this phenotype confers sensitivity to PARP inhibitors and platinum-therapies. Somatic reversion mutations restoring BRCA1/2 function mediate resistance, and have exclusively been reported in BRCA-associated tumors. In this study, we analyze matched tumor and normal sequencing from 31,927 patients and identify 846 (2.7%) patients with germline BRCA1/2 variants across 43 different cancer types, including 11 with somatic reversion mutations. While nine are in BRCA-associated tumors, we find two reversion mutations in non-BRCA-associated histologies, namely lung and esophagogastric adenocarcinomas. Both were detected following platinum therapy. Whole exome sequencing confirms the homologous recombination deficiency phenotype of these tumors. While reversion mutations arise in all BRCA-associated cancer types, here we show that reversion mutations arising post-platinum in non-BRCA associated histologies, while rare, may indicate BRCA1/2 mediated tumorigenesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.